Multicenter, Randomized, Double‐Blind Study Protocol Using Human Spinal Cord Recording Comparing Safety, Efficacy, and Neurophysiological Responses Between Patients Being Treated With Evoked Compound Action Potential–Controlled Closed‐Loop Spinal Cord Stimulation or Open‐Loop Spinal Cord Stimulation (the Evoke Study)

2019 ◽  
Vol 22 (3) ◽  
pp. 317-326 ◽  
Author(s):  
Robert Levy ◽  
Timothy R. Deer ◽  
Lawrence Poree ◽  
Steven M. Rosen ◽  
Leonardo Kapural ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Stimulation ◽  
Closed Loop ◽  
Compound Action Potential ◽  
Open Loop ◽  
Double Blind Study ◽  
Double Blind ◽  
Human Spinal Cord ◽  
Evoked Compound Action Potential ◽  
Compound Action

scholarly journals A New Direction for Closed-Loop Spinal Cord Stimulation: Combining Contemporary Therapy Paradigms with Evoked Compound Action Potential Sensing

2021 ◽  
Vol Volume 14 ◽  
pp. 3909-3918
Author(s):  
Ricardo Vallejo ◽  
Krishnan Chakravarthy ◽  
Andrew Will ◽  
Karen Trutnau ◽  
David Dinsmoor
Keyword(s):  
Spinal Cord ◽  
Action Potential ◽  
Spinal Cord Stimulation ◽  
Closed Loop ◽  
Compound Action Potential ◽  
Evoked Compound Action Potential ◽  
Compound Action

Randomized, Double-Blind Trial of Evoked Compound Action Potential (ECAP)-Controlled Closed-Loop Spinal Cord Stimulation for Patients With Chronic Trunk and/or Limb Pain

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Steven M Falowski
Keyword(s):  
Spinal Cord ◽  
Back Pain ◽  
Spinal Cord Stimulation ◽  
Closed Loop ◽  
Open Loop ◽  
Therapeutic Window ◽  
Double Blind ◽  
Objective Evidence ◽  
Patient Reported ◽  
Compound Action

Abstract INTRODUCTION Spinal cord stimulation (SCS) is a well-established treatment for chronic pain. Advancements in SCS systems have focused on eliminating paresthesias, but long-term success rates remain suboptimal. Variability in spinal cord (SC) activation with open-loop systems results in unpredictable inhibition of pain processing pathways, and may limit the efficacy of SCS. We report the first randomized, double-blind, pivotal study of SCS and the first therapy to measure real-time in Vivo SC neurophysiology using evoked compound action potentials (ECAPs). This study provides comparative efficacy and safety of ECAP-controlled closed-loop (CL) feedback stimulation compared to open-loop (OL) stimulation, and objective evidence of the mechanism of action of SCS. METHODS A total of 134 subjects were randomized into OL or CL. Subjects and the clinical staff were blinded to the treatment assignment. Both groups received the same device. Programming was equivalent with the only difference being that the closed-loop feedback feature was enabled in the Investigational group. A pain assessment and other patient reported outcome measures per IMMPACT were collected. ECAPs were also collected in both groups to compare the magnitude of SC activation and the percentage of time within the therapeutic window. RESULTS The primary composite endpoint demonstrated superior results in overall pain responders (P = .005) for CL-SCS (82.3%) compared to OL-SCS (60.3%). In addition, all prespecified hierarchical endpoints demonstrated better outcomes in the CL group, with both back pain reduction (P = .015) and back pain responders (P = .003) demonstrating superiority. The magnitude of SC activation was 7 times greater for CL-SCS and CL subjects spend 50% more time within the therapeutic window. In both groups, subjects showed improvements across disability, psychological, sleep, quality of life, and satisfaction. CONCLUSION ECAP-controlled closed-loop SCS has demonstrated superior overall pain relief compared to open-loop SCS. The study has just completed the primary outcome data analysis.

scholarly journals Defining the Therapeutic Window (TW) for Spinal Cord Stimulation (SCS) Using Evoked Compound Action Potential (ECAP) Recordings: Results From the Evoke Study

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Robert M Levy
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Stimulation ◽  
Closed Loop ◽  
Compound Action Potential ◽  
Open Loop ◽  
Therapeutic Window ◽  
Perception Threshold ◽  
Electrical Field Strength ◽  
Evoked Compound Action Potential

Abstract INTRODUCTION Spinal cord stimulation (SCS) is an established treatment for chronic pain; however, long-term success remains suboptimal. Current SCS therapies are fixed-output and do not account for large variation in electrical field strength due to changes in distance between the electrode and spinal cord (SC). METHODS In Avalon, 50 subjects were implanted and programmed in closed-loop; in Evoke, 134 subjects were randomized into open-loop (OL-SCS) or closed-loop (CL-SCS). ECAPs, a measure of SC activation, are recorded following each stimulation pulse in both groups. Each subject's therapeutic window (TW) is determined individually as the ECAP amplitude range between sensation perception threshold and discomfort. Without a measure of SC activation (eg, ECAPs), TW can only be based on perception of intensity; however, stimulation can produce variable SC activation (ECAP amplitude) as the electrode to SC distance varies with movement. RESULTS In the Evoke Study, each subjects' TW was determined in the clinic, along with the clinician prescribed level. There was no statistical difference between the 2 groups' TWs; however, CL-SCS subjects spent significantly more time in the TW despite having equivalent therapeutic ranges. Long-term data showed a similar percentage of stimuli in the TW (83%-97%). CONCLUSION TW can be individually defined by ECAP amplitudes (measure of SC activation), removing the need to rely on subjective reports of intensity, which can vary over time and with movement.

Cervical Spinal Cord Stimulation for Spasticity in Cerebral Palsy

Neurosurgery ◽  
1988 ◽  
Vol 22 (4) ◽  
pp. 707-714 ◽  
Author(s):  
Herman Hugenholtz ◽  
Peter Humphreys ◽  
William M. J. McIntyre ◽  
Robert A. Spasoff ◽  
Kate Steel
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Stimulation ◽  
Cervical Spinal Cord ◽  
Fine Motor ◽  
Base Line ◽  
Double Blind Study ◽  
Self Assessment ◽  
Double Blind ◽  
Chronic Stimulation ◽  
High Cervical

Abstract A prospective double-blind study of high cervical spinal cord stimulation conducted in eight moderately disabled, spastic, cerebral palsied children failed to demonstrate any significant improvement over base line function during chronic spinal cord stimulation at either optimal stimulation parameters or random placebo parameters. Chronic stimulation included 4 consecutive months of stimulation for 24 hours each day. Stimulators were randomly programmed at optimal parameters for 2 of the 4 months and at placebo parameters for the remaining 2 months. At the end of each month of chronic stimulation, subjects were assessed with a multidisciplinary test battery that included a self-assessment, specific clinical examinations, tests of gross and fine motor control, neuropsychological and neurophysiological tests, a detailed gait analysis, and video recordings. By 6 months after the completion of the study, only 1 of the 8 subjects continued to use his stimulator on a regular basis, with minimal benefit.

Spinal Cord Stimulation-induced Analgesia

2010 ◽  
Vol 113 (6) ◽  
pp. 1392-1405 ◽  
Author(s):  
Yun Guan ◽  
Paul W. Wacnik ◽  
Fei Yang ◽  
Alene F. Carteret ◽  
Chih-Yang Chung ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Action Potential ◽  
Spinal Cord Stimulation ◽  
Neuronal Response ◽  
Compound Action Potential ◽  
Dorsal Column ◽  
Conditioning Stimulation ◽  
Wdr Neurons ◽  
Sites Of Action ◽  
Compound Action

Background The sites of action and cellular mechanisms by which spinal cord stimulation reduces neuropathic pain remain unclear. Methods We examined the effect of bipolar electrical-conditioning stimulation (50 Hz, 0.2 ms, 5 min) of the dorsal column and lumbar dorsal roots on the response properties of spinal wide dynamic range (WDR) neurons in rats after L5 spinal nerve injury. The conditioning stimulation intensity was set at the lowest current that evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ- or C-compound action potential. Results Within 15 min of the dorsal column or root conditioning stimulation, the spontaneous activity rate of WDR neurons was significantly reduced in nerve-injured rats. Conditioning stimulation also significantly attenuated WDR neuronal responses to mechanical stimuli in nerve-injured rats and inhibited the C-component of the neuronal response to graded intracutaneous electrical stimuli applied to the receptive field in nerve-injured and sham-operated rats. It is noteworthy that dorsal column stimulation blocked windup of WDR neuronal response to repetitive intracutaneous electrical stimulation (0.5 Hz) in nerve-injured and sham-operated rats, whereas dorsal root stimulation inhibited windup only in sham-operated rats. Therefore, stimulation of putative spinal substrates at A-fiber intensities with parameters similar to those used by patients with spinal cord stimulators attenuated established WDR neuronal hyperexcitability in the neuropathic condition and counteracted activity-dependent increase in neuronal excitability (i.e., windup). Conclusions These results suggest a potential cellular mechanism underlying spinal cord stimulation-induced pain relief. This in vivo model allows the neurophysiologic basis for spinal cord stimulation-induced analgesia to be studied.

scholarly journals The Evoked Compound Action Potential as a Predictor for Perception in Chronic Pain Patients: Tools for Automatic Spinal Cord Stimulator Programming and Control

2021 ◽  
Vol 15 ◽  
Author(s):  
Julie G. Pilitsis ◽  
Krishnan V. Chakravarthy ◽  
Andrew J. Will ◽  
Karen C. Trutnau ◽  
Kristin N. Hageman ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Action Potential ◽  
Pulse Width ◽  
Growth Curves ◽  
Compound Action Potential ◽  
Novel Approach ◽  
Technological Advances ◽  
Evoked Compound Action Potential ◽  
Compound Action

ObjectivesSpinal cord stimulation (SCS) is a drug free treatment for chronic pain. Recent technological advances have enabled sensing of the evoked compound action potential (ECAP), a biopotential that represents neural activity elicited from SCS. The amplitudes of many SCS paradigms – both sub- and supra-threshold – are programmed relative to the patient’s perception of SCS. The objective of this study, then, is to elucidate relationships between the ECAP and perception thresholds across posture and SCS pulse width. These relationships may be used for the automatic control and perceptually referenced programming of SCS systems.MethodsECAPs were acquired from 14 subjects across a range of postures and pulse widths with swept amplitude stimulation. Perception (PT) and discomfort (DT) thresholds were recorded. A stimulation artifact reduction scheme was employed, and growth curves were constructed from the sweeps. An estimate of the ECAP threshold (ET), was calculated from the growth curves using a novel approach. Relationships between ET, PT, and DT were assessed.ResultsETs were estimated from 112 separate growth curves. For the postures and pulse widths assessed, the ET tightly correlated with both PT (r = 0.93; p < 0.0001) and DT (r = 0.93; p < 0.0001). The median accuracy of ET as a predictor for PT across both posture and pulse width was 0.5 dB. Intra-subject, ECAP amplitudes at DT varied up to threefold across posture.ConclusionWe provide evidence that the ET varies across both different positions and varying pulse widths and suggest that this variance may be the result of postural dependence of the recording electrode-tissue spacing. ET-informed SCS holds promise as a tool for SCS parameter configuration and may offer more accuracy over alternative approaches for neural and perceptual control in closed loop SCS systems.

scholarly journals Platform for Closed Loop Neuromodulation Based on Dual Mode Biosignals

2017 ◽  
Author(s):  
Khalid B. Mirza ◽  
Nishanth Kulasekeram ◽  
Simon Cork ◽  
Stephen Bloom ◽  
Konstantin Nikolic ◽  
...  
Keyword(s):  
Closed Loop ◽  
Compound Action Potential ◽  
Open Loop ◽  
Neural Stimulation ◽  
Appetite Control ◽  
Chemical Signatures ◽  
Signal Mode ◽  
On Chip ◽  
Final System ◽  
Compound Action

AbstractClosed loop neuromodulation, where the stimulation is controlled autonomously based on physiological events, has been more effective than open loop techniques. In the few existing closed loop implementations which have a feedback, indirect non-neurophysiological biomarkers have been typically used (e.g. heart rate, stomach distension). Although these biomarkers enable automatic initiation of neural stimulation, they do not enable intelligent control of stimulation dosage. In this paper, we present a novel closed loop neuromodulation platform based on a dual signal mode that is detecting electrical and chemical signatures of neural activity. We demonstrated it on a case of vagus nerve stimulation (VNS). Vagal chemical (pH) signal is detected and used for initiatisng VNS and vagal compound action potential (CAP) signals are used to determine the stimulation dosage and pattern. Although we used the paradigm of appetite control and neurometabolic therapies, the platform developed here can be utilised for prototyping closed loop neuromodulation systems before adapting the final System-on-Chip (SoC) design.

scholarly journals Effect of Chronological Age on Pulse Rate Discrimination in Adult Cochlear-Implant Users

2021 ◽  
Vol 25 ◽  
pp. 233121652110073
Author(s):  
Kelly C. Johnson ◽  
Zilong Xie ◽  
Maureen J. Shader ◽  
Paul G. Mayo ◽  
Matthew J. Goupell
Keyword(s):  
Pulse Rate ◽  
Compound Action Potential ◽  
Action Potential Amplitude ◽  
Growth Functions ◽  
Evoked Compound Action Potential ◽  
Rate Discrimination ◽  
Amplitude Growth ◽  
Temporal Pulse ◽  
Compound Action Potential Amplitude ◽  
Compound Action

Cochlear-implant (CI) users rely heavily on temporal envelope cues to understand speech. Temporal processing abilities may decline with advancing age in adult CI users. This study investigated the effect of age on the ability to discriminate changes in pulse rate. Twenty CI users aged 23 to 80 years participated in a rate discrimination task. They attempted to discriminate a 35% rate increase from baseline rates of 100, 200, 300, 400, or 500 pulses per second. The stimuli were electrical pulse trains delivered to a single electrode via direct stimulation to an apical (Electrode 20), a middle (Electrode 12), or a basal location (Electrode 4). Electrically evoked compound action potential amplitude growth functions were recorded at each of those electrodes as an estimate of peripheral neural survival. Results showed that temporal pulse rate discrimination performance declined with advancing age at higher stimulation rates (e.g., 500 pulses per second) when compared with lower rates. The age-related changes in temporal pulse rate discrimination at higher stimulation rates persisted after statistical analysis to account for the estimated peripheral contributions from electrically evoked compound action potential amplitude growth functions. These results indicate the potential contributions of central factors to the limitations in temporal pulse rate discrimination ability associated with aging in CI users.

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